Document Detail


Novel deletion of RPL15 identified by array-comparative genomic hybridization in Diamond-Blackfan anemia.
MedLine Citation:
PMID:  23812780     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Diamond-Blackfan anemia (DBA) is an inherited red blood cell aplasia that usually presents during the first year of life. The main features of the disease are normochromic and macrocytic anemia, reticulocytopenia, and nearly absent erythroid progenitors in the bone marrow. The patients also present with growth retardation and craniofacial, upper limb, heart and urinary system congenital malformations in ~30-50 % of cases. The disease has been associated with point mutations and large deletions in ten ribosomal protein (RP) genes RPS19, RPS24, RPS17, RPL35A, RPL5, RPL11, RPS7, RPS10, RPS26, and RPL26 and GATA1 in about 60-65 % of patients. Here, we report a novel large deletion in RPL15, a gene not previously implicated to be causative in DBA. Like RPL26, RPL15 presents the distinctive feature of being required both for 60S subunit formation and for efficient cleavage of the internal transcribed spacer 1. In addition, we detected five deletions in RP genes in which mutations have been previously shown to cause DBA: one each in RPS19, RPS24, and RPS26, and two in RPS17. Pre-ribosomal RNA processing was affected in cells established from the patients bearing these deletions, suggesting a possible molecular basis for their pathological effect. These data identify RPL15 as a new gene involved in DBA and further support the presence of large deletions in RP genes in DBA patients.
Authors:
Michael Landowski; Marie-Françoise O'Donohue; Christopher Buros; Roxanne Ghazvinian; Nathalie Montel-Lehry; Adrianna Vlachos; Colin A Sieff; Peter E Newburger; Edyta Niewiadomska; Michal Matysiak; Bertil Glader; Eva Atsidaftos; Jeffrey M Lipton; Alan H Beggs; Pierre-Emmanuel Gleizes; Hanna T Gazda
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2013-06-30
Journal Detail:
Title:  Human genetics     Volume:  132     ISSN:  1432-1203     ISO Abbreviation:  Hum. Genet.     Publication Date:  2013 Nov 
Date Detail:
Created Date:  2013-10-15     Completed Date:  2013-12-02     Revised Date:  2014-11-04    
Medline Journal Info:
Nlm Unique ID:  7613873     Medline TA:  Hum Genet     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  1265-74     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Anemia, Diamond-Blackfan / genetics*
Comparative Genomic Hybridization
DNA Copy Number Variations
Gene Deletion*
Gene Knockdown Techniques
HeLa Cells
Humans
Mutation
RNA, Ribosomal / analysis,  genetics
RNA, Small Interfering
Ribosomal Proteins / genetics*,  metabolism
Grant Support
ID/Acronym/Agency:
K02 HL111156/HL/NHLBI NIH HHS; K02 HL111156/HL/NHLBI NIH HHS; R01 HL079571/HL/NHLBI NIH HHS; R01 HL107558/HL/NHLBI NIH HHS; R01 HL107558/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/RNA, Ribosomal; 0/RNA, Small Interfering; 0/Ribosomal Proteins; 0/ribosomal protein L15
Comments/Corrections

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